Cachexie et obésité dans la maladie pulmonaire obstructive chronique : une question de déséquilibre?

La maladie pulmonaire obstructive chronique (MPOC) est un trouble respiratoire qui amène également des effets systémiques tels que de l'inflammation chronique. Cet effet extrapulmonaire semblerait être le facteur central du développement de la perte de poids et de comorbidités diverses. La perte de poids et plus particulièrement la perte de masse musculaire, sont reliées à un faible taux de survie et leurs mécanismes sont toujours inconnus. Cependant, plusieurs hypothèses ont été émises sur le sujet. Un déséquilibre systémique des facteurs anaboliques/catabolîques en faveur du catabolisme ainsi qu'un déséquilibre énergétique négatif associé à un hypermétabolisme et/ou à une dénutrition sont des causes explicatives potentielles signalées dans la littérature. Leurs contributions respectives n'avaient jamais été étudiées dans la MPOC et sont l'objet de la première partie ce travail. Nous avons démontré que l'atrophie musculaire pouvait être reliée à l'activation concomitante d'un signal de dégradation protéique et d'un signal de synthèse protéique musculaire possiblement déficient. De plus, l'inactivité associée à la MPOC prédisposerait le quadriceps à un déséquilibre des signaux cataboliques/anaboliques en faveur d'un catabolisme favorisant ainsi le développement d'atrophie musculaire. Nous avons aussi mis en évidence la présence d'un hypermétabolisme chez des patients MPOC qui s'expliquerait, entre autres, par l'activation du système nerveux sympathique. L'ensemble de ces résultats suggère qu'un amalgame de facteurs favorisant le catabolisme musculaire amènerait inévitablement le patient vers de la cachexie. En plus d'un état de perte de poids, l'augmentation de la fréquence de l'obésité dans cette maladie inquiète. Les effets néfastes que pourrait avoir l'obésité chez le patient MPOC sont l'objet de la deuxième partie de ce travail. Nous avons démontré la présence de plusieurs anormalités métaboliques et inflammatoires chez les patients MPOC obèses. De plus, la fréquence plus élevée du syndrome métabolique retrouvée chez ceux-ci pourrait favoriser le développement de comorbidités graves. En conclusion, tant l'atrophie musculaire que l'obésité ont un impact important sur l'évolution clinique de la MPOC et la compréhension de leurs mécanismes aidera à la mise en place de stratégies thérapeutiques efficaces et mieux ciblées

Metabolic and inflammatory profile in obese patients with chronic obstructive pulmonary disease

Background: Overweight and obesity have been associated with better survival in patients with chronic obstructive pulmonary disease (COPD). On the other hand, excess body weight is associated with abnormal metabolic and inflammatory profiles that define the metabolic syndrome and predispose to cardiovascular diseases. This study was undertaken to evaluate the impact of overweight and obesity on the prevalence of the metabolic syndrome and on the metabolic and inflammatory profiles in patients with COPD. Methods: Twenty-eight male patients with COPD were divided into an overweight/obese group [n 16, body mass index (BMI) 33.5 4.2 kg/m2] and normal weight group (n 12, BMI 21.1 2.6 kg/m2). Anthropometry, pulmonary function and body composition were assessed. The metabolic syndrome was diagnosed according to waist circumference, circulating levels of triglyceride and high-density lipoprotein cholesterol levels, fasting glycemia and blood pressure. C-reactive protein, tumor necrosis factor- (TNF-), interleukin-6 (IL-6), leptin and adiponectin plasma levels were measured. Results: Airflow obstruction was less severe in overweight/obese compared with normal weight patients (forced expiratory volume1: 51 19% versus 31 12% predicted, respectively, P 0.01). The metabolic syndrome was diagnosed in 50% of overweight/obese patients and in none of the normal weight patients. TNF-, IL-6 and leptin were significantly higher in overweight/obese patients whereas the adiponectin levels were reduced in the presence of excess weight. Conclusions: The metabolic syndrome was frequent in overweight/obese patients with COPD. Obesity in COPD was associated with a spectrum of metabolic and inflammatory abnormalities

Incidence, Prevalence, and Mortality Trends in Chronic Obstructive Pulmonary Disease over 2001 to 2011: A Public Health Point of View of the Burden

Background. An increase of chronic obstructive pulmonary disease (COPD) prevalence was reported in Canada despite the decline of the main risk factor. Objectives. To estimate incidence, prevalence, and mortality of COPD from 2001 to 2011 and establish the COPD burden by the evaluation of the age-period-cohort effects on incidence trends and the comorbidities prevalence estimations. Methods. A retrospective population-based cohort was built using Quebec health administrative data. Change in trends was measured by relative percentage of changes and by joinpoint regression. After a descriptive analysis of the trends, an age-period-cohort analysis was performed on incidence rates. Results. Overall increase in prevalence along with a decrease of incidence and all-cause mortality was observed. Over time, all age-standardized trends were higher in men than women. Despite higher rates, the number of incident and prevalent cases in women exceeds men since 2004. The curve analysis by age groups showed over time a downshift for both sexes in incidence and all-cause mortality. Further analysis showed the presence of a cohort effect in women. Conclusion. The burden of COPD has risen over time. Women younger than 65 years old have been identified as at-risk group for healthcare planning

Understanding the evolution of multimorbidity : evidences from the North West Adelaide Health Longitudinal Study

Objective: The aim of this study is to describe the evolution of multimorbidity. Study Design and Setting: Data from 1854 South Australians who participated in the North West Adelaide longitudinal Health Study(NWAHS) was collected between baseline (2000–2002) and follow-up (2008–2010). Status for eight chronic diseases (CDs) was determined by biomedical measurement or self-report. Chronic disease (CD) mean age of occurrence and order of appearance was investigated. Results: The prevalence of multimorbidity increased from 32% to 64% during the 7.861.1 years of follow-up. The estimated mean age of onset of a new CD was significantly older for hypertension, cardiovascular disease (CVD) and chronic obstructive pulmonary disease (COPD) and younger for hypercholesterolemia, asthma and other mental problem. Hypercholesterolemia was more likely to develop as a first than as a subsequent CD (39%vs.16%, p,0.0001) while CVD (1%vs.5%, p,0.0001), diabetes (5%vs.11%, p,0.001) and COPD (6%vs.16%, p,0.0001) were less likely. The presence of mood disorders at baseline was associated with an increased risk of developing other mental disorders (36%vs.12%, p, 0.0001), diabetes (18%vs.9%, p,0.01) and asthma (30%vs.21%, p,0.05). Conclusion: Longitudinal data could be used to study the evolution of multimorbidity and could provide information on CDs mean age of occurrence, order of appearance and impact on the development of future CDs

Chronic Obstructive Pulmonary Disease in Women

BACKGROUND: Little is known about the comparative impact of chronic obstructive pulmonary disease (COPD) between women and men and about women’s response to pulmonary rehabilitation

The effect of obesity on chronic respiratory diseases: pathophysiology and therapeutic strategies

Sedentary lifestyles and increased pollution brought about by industrialization pose major challenges to the prevention of both obesity and chronic respiratory diseases such as chronic obstructive pulmonary disease (COPD), asthma, obstructive sleep apnea and obesity hypoventilation syndrome. Obesity has emerged as an important risk factor for these respiratory diseases, and in many instances weight loss is associated with important symptomatic improvement. Moreover, obesity may influence the development and presentation of these diseases. In this article, we review the current understanding of the influence of obesity on chronic respiratory diseases and the clinical management of obesity concurrent with asthma, COPD, obstructive sleep apnea or obesity hypoventilation syndrome

Muscle atrophy and hypertrophy signaling in patients with chronic obstructive pulmonary disease

Rationale: The molecular mechanisms of muscle atrophy in chronic obstructive pulmonary disease (COPD) are poorly understood. In wasted animals, muscle mass is regulated by several AKT-related signaling pathways. Objectives: To measure the protein expression of AKT, forkhead box class O (FoxO)-1 and -3, atrogin-1, the phosphophrylated form of AKT, p70S6K glycogen synthase kinase-3&szlig; (GSK-3&szlig;), eukaryotic translation initiation factor 4E binding protein-1 (4E-BP1), and the mRNA expression of atrogin-1, muscle ring finger (MuRF) protein 1, and FoxO-1 and -3 in the quadriceps of 12 patients with COPD with muscle atrophy and 10 healthy control subjects. Five patients with COPD with preserved muscle mass were subsequently recruited and were compared with six patients with low muscle mass.Methods: Protein contents and mRNA expression were measured by Western blot and quantitative polymerase chain reaction, respectively.Measurements and Main Results: The levels of atrogin-1 and MuRF1 mRNA, and of phosphorylated AKT and 4E-BP1 and FoxO-1 proteins, were increased in patients with COPD with muscle atrophy compared with healthy control subjects, whereas atrogin-1, p70S6K, GSK-3&szlig;, and FoxO-3 protein levels were similar. Patients with COPD with muscle atrophy showed an increased expression of p70S6K, GSK-3&szlig;, and 4E-BP1 compared with patients with COPD with preserved muscle mass.Conclusions: An increase in atrogin-1 and MuRF1 mRNA and FoxO-1 protein content was observed in the quadriceps of patients with COPD. The transcriptional regulation of atrogin-1 and MuRF1 may occur via FoxO-1, but independently of AKT. The overexpression of the muscle hypertrophic signaling pathways found in patients with COPD with muscle atrophy could represent an attempt to restore muscle mass.<br /